MACROPHAGE-INDUCED ENHANCEMENT OF ENDOGENOUS TUMOR LYSOSOME ACTIVITY

Google Scholar
  • 1 January 1981
    • journal article
    • research article
    • Vol. 41  (6) , 2221-2229
Abstract
Activated macrophages have the capacity to selectively injure neoplastic cells. Previous morphological observations suggest that the final effectors of macrophage-mediated tumor cytotoxicity are lysosomes of activated macrophage origin which are translocated directly into susceptible target cells. An attempt was made to quantitatively determine if elevated levels of specific lysosomal activity are present in tumor cells exposed to activated macrophages in vitro. Effector macrophages were obtained from the peritoneal cavities of glucan-treated mice. Target cells were tumorigenic and nontumorigenic fibroblast cell lines derived from the same 2 strains. Macrophage-dependent target cell cytotoxicity was quantitated using [3H]thymidine incorporation inhibition and 51Cr postlabeling assays. Tumor lysosome activity was quantitated using newly developed microspectrophotometric assays for the lysosomal hydrolase acid phosphatase and for the lysosomotropic probe acridine orange. The specific lysosomal activity of tumor target cells correlates directly with the degree of tumor cytotoxicity generated by effector macrophages. This macrophage-induced elevation of tumor lysosome activity does not appear to represent the acquisition of macrophage-derived organelles; rather, it appears to represent an increase in the number of size of intact, endogenous tumor lysosomes due to macrophage-dependent reduction of tumor cell density. Clinically proven tumor growth-reducing regimens such as host macrophage activation may be useful adjuncts to cancer therapies designed to selectively promote and labilize tumor cell lysosomes.